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TitleStructure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome.
Journal, issue, pagesMol Cell, Vol. 82, Issue 13, Page 2505-22518.e7, Year 2022
Publish dateJul 7, 2022
AuthorsPiotr Gerlach / William Garland / Mahesh Lingaraju / Anna Salerno-Kochan / Fabien Bonneau / Jérôme Basquin / Torben Heick Jensen / Elena Conti /
PubMed AbstractIn mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The nuclear exosome targeting ...In mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The nuclear exosome targeting (NEXT) complex plays a central role in directing non-functional transcripts to exosome-mediated degradation, but the structural and molecular mechanisms remain enigmatic. Here, we elucidated the architecture of the human NEXT complex, showing that it exists as a dimer of MTR4-ZCCHC8-RBM7 heterotrimers. Dimerization preconfigures the major MTR4-binding region of ZCCHC8 and arranges the two MTR4 helicases opposite to each other, with each protomer able to function on many types of RNAs. In the inactive state of the complex, the 3' end of an RNA substrate is enclosed in the MTR4 helicase channel by a ZCCHC8 C-terminal gatekeeping domain. The architecture of a NEXT-exosome assembly points to the molecular and regulatory mechanisms with which the NEXT complex guides RNA substrates to the exosome.
External linksMol Cell / PubMed:35688157 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 9.5 Å
Structure data

14510

7z4y

EMDB-14510, PDB-7z4y:
Human NEXT dimer - overall reconstruction of the core complex
Method: EM (single particle) / Resolution: 4.5 Å

14511

7z4z

EMDB-14511, PDB-7z4z:
Human NEXT dimer - focused reconstruction of the dimerization module
Method: EM (single particle) / Resolution: 4.0 Å

14513

7z52

EMDB-14513, PDB-7z52:
Human NEXT dimer - focused reconstruction of the single MTR4
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-14514: Human NEXT dimer - single protomer
Method: EM (single particle) / Resolution: 6.8 Å

EMDB-14515: Human NEXT dimer in complex with the nuclear RNA exosome
Method: EM (single particle) / Resolution: 9.5 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsRNA BINDING PROTEIN / HELICASE / ATPASE / RNA DEGRADATION / EXOSOME

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